IgG is a heterotetramer composed of two heavy chains and two light chains held together by disulfide bonds forming three protein domains separated by a flexible and protease sensitive hinge region. The two identical Fab portions bind antigens and the single Fc portion is responsible for effector functions, including binding and activation of complement factor C1q and Fc receptors on leukocytes.
In addition to the polypeptide backbone the Fc portion contains a conserved glycan on each heavy chain attached to Asn-297. This oligosaccharide is of the complex biantennary type with a core fucose linked to the innermost N-acetylglucosamine (GlcNAc). These glycans are located in the interface between the CH2 domains (second constant domain of the heavy chains).
EndoS is an endoglycosidase secreted by the human pathogen Streptococcus pyogenes. EndoS specifically hydrolyzes the asparagine-linked glycan on IgG between the two core GlcNAc residues. In contrast to many related endoglycosidases that require or are enhanced by denaturation of the glycoprotein substrate, EndoS only hydrolyzes native IgG. No other substrate for EndoS has been found to date.